α-β-Unsaturated Sulfonamides
Cancer remains a leading-cause of mortality in the United States and in the world. To be useful, a new chemotherapeutic agent should have a wide spectrum of activity and significant therapeutic index. Styrene-ω-sulfonanilide has been prepared by reacting styrylsulfonyl chloride with aniline (Bordwell et al., J. Amer. Chem. Soc. 68:139, 1946). This and certain other styrene-ω-sulfonanilides have been prepared by Knoevenagel-type synthesis as possible chemosterilants against the common house fly Musca domestica L. (Oliver et al., Synthesis 321–322, 1975).
U.S. Pat. No. 4,035,421 to Snyder, Jr. describes the preparation of N-(3,4-dichlorophenyl)-2-phenylethenesulfonamide and its use as an antibacterial agent.
The styrene-ω-sulfonanilides 3′-hydroxy-4-nitrostyrene-β-sulfonanilide, 3′-hydroxy-2-nitrostyrene-β-sulfonanilide and 5′-hydroxy-2′-methyl-4-nitrostyrene-β-sulfonanilide were utilized as intermediates in the preparation of certain stilbenes by Waldau et al. Angew. Chem., Int. Ed. Engl. 11(9):826–8 (1972). The styrene-ω-sulfonanilides 3′-hydroxy-3-nitrostyrene-β-sulfonanilide and 5′-hydroxy-2′-methyl-4-nitrostyrene-β-sulfonanilide have been utilized in the preparation of stilbenes used as dyes (DE 2118493-Farbenfab AG).
Aswarthamma et al., Chimica Acta Turcica 24:7–10 (1996) disclose the preparation of certain trans-(1-aryl-(2-anilinesulphonyl)ethylenes. No biological activity is set forth for the compounds. Touarti et al., J. Soc. Alger. Chim. 6(1):39–52 (1996) disclose the preparation of certain α,β-unsaturated sulfonamides for inhibition of coniferyl alcohol dehydrogenase (CADH).
Except for the isolated teaching of antibacterial activity of N-(3,4-dichlorophenyl)-2-phenylethenesulfonamide, no useful pharmaceutical activity has been proposed for the limited numbers of α,β-unsaturated sulfonamides known to the prior art. In particular, no anti-cell proliferation or anticancer utility has been proposed for this class of compounds.
New cell antiproliferative agents, and anticancer therapeutics in particular, are needed which are useful in inhibiting proliferation of and/or killing cancer cells. In particular, such agents are needed which are selective in the killing of proliferating cells such as tumor cells, but not normal cells. Antineoplasitc agents are needed which are effective against a broad range of tumor types.